U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 947128251 274 PADYRCPISLELMRDPVVVATGQTYDRASIKLWMDSGHNTCPKTGQTLSHTEL 326
Cdd:cd16664    1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNTCPITGQPLTHTDL 53

N-terminal domain of mixed lineage kinase domain-like protein (MLKL) and similar proteins; MLKL is a pseudokinase that does not have protein kinase activity and plays a key role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process. The model corresponds to the MLKL N-terminal region that reveals a four-helix bundle with an additional helix at the top which is likely key for MLKL function. The N-terminal domain binds directly to phospholipids and induces membrane permeabilization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 947128251  60 IRKTQLLGVVFEELVRvSNLNSNSSVLFLCLEEMYIVLHNIKILIEDFSNGSKFNLLMQIETVADNFHRLTGELSTLLDV 139
Cdd:cd21037   28 AERVAELLLALEELLE-GKEEDLSPELREALEELERTLEEIKEFVEKISKRSRLKRFLKAKSIAEKLEELNERLDDALQL 106

                 ....
gi 947128251 140 LPLQ 143
Cdd:cd21037  107 FQLA 110

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 947128251 274 PADYRCPISLELMRDPVVVATGQTYDRASIKLWMDSGHNTCPKTGQTLSHTEL 326
Cdd:cd16664    1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNTCPITGQPLTHTDL 53

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 947128251  273 IPADYRCPISLELMRDPVVVATGQTYDRASIKLWMDSGHNTCPKTGQTLSHTELIPNRVLRNMIAAWCREQRI 345
Cdd:pfam04564   1 IPDEFLDPITFELMTDPVILPSGITYDRSTIERHLLSVDPTDPFTREPLTHDQLIPNLELKAKIDAWLEEKRW 73

N-terminal domain of mixed lineage kinase domain-like protein (MLKL) and similar proteins; MLKL is a pseudokinase that does not have protein kinase activity and plays a key role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process. The model corresponds to the MLKL N-terminal region that reveals a four-helix bundle with an additional helix at the top which is likely key for MLKL function. The N-terminal domain binds directly to phospholipids and induces membrane permeabilization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 947128251  60 IRKTQLLGVVFEELVRvSNLNSNSSVLFLCLEEMYIVLHNIKILIEDFSNGSKFNLLMQIETVADNFHRLTGELSTLLDV 139
Cdd:cd21037   28 AERVAELLLALEELLE-GKEEDLSPELREALEELERTLEEIKEFVEKISKRSRLKRFLKAKSIAEKLEELNERLDDALQL 106

                 ....
gi 947128251 140 LPLQ 143
Cdd:cd21037  107 FQLA 110

U-box domain, a modified RING finger, found in Arabidopsis plant U-box proteins (AtPUB) and similar proteins; The plant PUB proteins, also known as U-box domain-containing proteins, are much more numerous in Arabidopsis which has 62 in comparison with the typical 6 in most animals. The majority of AtPUBs in this subfamily are known as ARM domain-containing PUB proteins, containing a C-terminally-located, tandem ARM (armadillo) repeat protein-interaction region in addition to the U-box domain. They have been implicated in the regulation of cell death and defense. They also play important roles in other plant-specific pathways, such as controlling both self-incompatibility and pseudo-self-incompatibility, as well as acting in abiotic stress. A subgroup of ARM domain-containing PUB proteins harbors a plant-specific U-box N-terminal domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|...
gi 947128251 274 PADYRCPISLELMRDPVVVATGQTYDRASIKLWMDSGHNTCPKTGQTLSHTEL 326
Cdd:cd16664    1 PEEFICPISLELMKDPVILATGQTYERAAIEKWLDSGNNTCPITGQPLTHTDL 53

U-box domain; The U-box is a domain of ~70 amino acids that is present in proteins from yeast to human. It consists of the beta-beta-alpha-beta-alpha- fold typical of U-box and RING domains. The central alpha helix is flanked by two prominent surface-exposed loop regions. This domain is one class of E3 ligases, involved in the ubiquitination process. This domain is related to the Ring finger pfam00097 but lacks the zinc binding residues.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 947128251  273 IPADYRCPISLELMRDPVVVATGQTYDRASIKLWMDSGHNTCPKTGQTLSHTELIPNRVLRNMIAAWCREQRI 345
Cdd:pfam04564   1 IPDEFLDPITFELMTDPVILPSGITYDRSTIERHLLSVDPTDPFTREPLTHDQLIPNLELKAKIDAWLEEKRW 73

U-box domain, a modified RING finger; The U-box protein family is a family of E3 enzymes that also includes the HECT family and the RING finger family. The E3 enzyme is ubiquitin-protein ligase that cooperates with a ubiquitin-activating enzyme (E1) and a ubiquitin-conjugating enzyme (E2), and plays a central role in determining the specificity of the ubiquitination system. It removes the ubiquitin molecule from the E2 enzyme and attaches it to the target substrate, forming a covalent bond between ubiquitin and the target. U-box proteins are characterized by the presence of a U-box domain of approximately 70 amino acids. The U-box is a modified form of the RING finger domain that lacks metal chelating cysteines and histidines. It resembles the cross-brace RING structure consisting of three beta-sheets and a single alpha-helix, which would be stabilized by salt bridges instead of chelated metal ions. U-box proteins are widely distributed among eukaryotic organisms and show a higher prevalence in plants than in other organisms.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 947128251 277 YRCPISLELMRDPVVVATGQTYDRASIKLWMDSgHNTCPKTGQTL 321
Cdd:cd16453    1 FLCPISGELMKDPVITPSGITYDRSAIERWLLS-DNTDPFTREPL 44

second U-box domain, a modified RING finger, found in Legionella pneumophila U-box protein LubX and similar proteins; LubX, also called RING-type E3 ubiquitin transferase LubX, is part of the large arsenal of effectors in Legionella pneumophila that are translocated into the host cytosol during infection. LubX acts as an E3 ubiquitin-protein ligase (EC 2.3.2.27) that interferes with the host's ubiquitination pathway. LubX contains two RING-like U-box domains. U-box 1 is critical to the ubiquitin ligase activity, and U-box 2 mediates interaction with host target. This model corresponds to the second one.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 947128251 274 PADYRCPISLELMRDPVVVATGQTYDRASIKLWMdSGHNTCPKTGQTLSHTELIPNRVLRNMIAAWCREQ 343
Cdd:cd23150    1 PDIFLCPISKTLIKTPVITAQGKVYDQEALSNFL-IATGNKDETGKKLSIDDVVVFDELYQQIKVYNFYR 69

SPL-RING finger found in E3 SUMO-protein ligase NSE2 and similar proteins; NSE2, also known as MMS21 homolog (MMS21) or non-structural maintenance of chromosomes element 2 homolog (Non-SMC element 2 homolog, NSMCE2), is an autosumoylating small ubiquitin-like modifier (SUMO) ligase required for the response to DNA damage. It regulates sumoylation and nuclear-to-cytoplasmic translocation of skeletal and heart muscle-specific variant of the alpha subunit of nascent polypeptide associated complex (skNAC)-Smyd1 in myogenesis. It is also required for resisting extrinsically induced genotoxic stress. Moreover, NSE2 together with its partner proteins SMC6 and SMC5 form a tight subcomplex of the structural maintenance of chromosomes SMC5-6 complex, which includes another two subcomplexes, NSE1-NSE3-NSE4 and NSE5-NSE6. SMC6 and NSE3 are sumoylated in an NSE2-dependent manner, but SMC5 and NSE1 are not. NSE2-dependent E3 SUMO ligase activity is required for efficient DNA repair, but not for SMC5-6 complex stability. NSE2 contains a RING variant known as a Siz/PIAS (protein inhibitor of activated signal transducer and activator of transcription)-like RING (SPL-RING) finger that is likely shared by the SP-RING type SUMO E3 ligases, such as PIAS family proteins. The SPL-RING finger is a variant of the RING finger, which lacks the second, fifth, and sixth zinc-binding residues of the consensus C3H2C3-/C3HC4-type RING fingers. It harbors only one Zn binding site and is required for the sumoylating activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 947128251 277 YRCPISLELMRDPVVVAT-GQTYDRASIKLWMDSGHNT--CPKTG--QTLSHTELIPNRVLRNMI 336
Cdd:cd16651    1 LKCPITQQLMVDPVRNKKcGHTYEKAAILQYLQSRKKKakCPVAGcrNTVSKSDLVPDPELKRRI 65

RING finger, HC subclass, found in tripartite motif-containing protein 35 (TRIM35) and similar proteins; TRIM35, also known as hemopoietic lineage switch protein 5 (HLS5), is a putative hepatocellular carcinoma (HCC) suppressor that inhibits phosphorylation of pyruvate kinase isoform M2 (PKM2), which is involved in aerobic glycolysis of cancer cells and further suppresses the Warburg effect and tumorigenicity in HCC. It also negatively regulates Toll-like receptor 7 (TLR7)- and TLR9-mediated type I interferon production by suppressing the stability of interferon regulatory factor 7 (IRF7). Moreover, TRIM35 regulates erythroid differentiation by modulating globin transcription factor 1 (GATA-1) activity. TRIM35 belongs to the C-IV subclass of the TRIM (tripartite motif) family of proteins that are defined by their N-terminal RBCC (RING, Bbox, and coiled coil) domains, including three consecutive zinc-binding domains, a C3HC4-type RING-HC finger, Bbox1 and Bbox2, and a coiled coil region, as well as a B30.2/SPRY (SplA and ryanodine receptor) domain positioned C-terminal to the RBCC domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 947128251 276 DYRCPISLELMRDPVVVATGQTYDRASIKL-WMDSGHNTCPKTGQTLSHTELIPNRVLRNMI 336
Cdd:cd16599    4 ELLCPICYEPFREAVTLRCGHNFCKGCVSRsWERQPRAPCPVCKEASSSDDLRTNHTLNNLV 65

U-box domain, a modified RING finger, found in pre-mRNA-processing factor 19 (Prp19) and similar proteins; Prp19, also known as nuclear matrix protein 200 (NMP200), senescence evasion factor (SNEV), or DNA repair protein Pso4 (psoralen-sensitive mutant 4), is a ubiquitously expressed multifunctional E3 ubiquitin ligase with pleiotropic activities in DNA damage signaling, repair, and replicative senescence. It functions as a critical component of DNA repair and DNA damage checkpoint complexes. It senses DNA damage, binds double-stranded DNA in a sequence-independent manner, facilitates processing of damaged DNA, promotes DNA end joining, regulates replication protein A (RPA2) phosphorylation and ubiquitination at damaged DNA, and regulates RNA splicing and mitotic spindle formation in its integral capacity as a scaffold for a multimeric core complex. Prp19 contains an N-terminal E3 ubiquitin ligase U-box domain with E2 recruitment function that facilitates dimerization and is essential for its auto-ubiquitination activity in vitro or when overexpressed, a coiled-coil Prp19 homology region that mediates its tetramerization and interaction with CDC5L and SPF27, and a C-terminal seven-bladed WD40 beta-propeller type of leucine-rich architectural repeats that form an asymmetrical barrel-shaped structure important for substrate recognition and recruitment.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|.
gi 947128251 279 CPISLELMRDPVV-VATGQTYDRASIKLWMDSgHNTCPKTGQTLSHTELIP 328
Cdd:cd16656    3 CAISGEVPEEPVVsPKSGHVFEKRLIEKYIAE-NGTDPVTGEPLTEEDLIE 52

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and similar proteins; TRAF6, also known as interleukin-1 signal transducer or RING finger protein 85 (RNF85), is a cytoplasmic adapter protein that mediates signals induced by the tumor necrosis factor receptor (TNFR) superfamily and Toll-like receptor (TLR)/interleukin-1 receptor (IL-1R) family. It functions as a mediator involved in the activation of mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K), and interferon regulatory factor pathways, as well as in IL-1R-mediated activation of NF-kappaB. TRAF6 is also an oncogene that plays a vital role in K-RAS-mediated oncogenesis. TRAF6 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and several zinc fingers, and a C-terminal TRAF domain that comprises a coiled coil domain and a conserved TRAF-C domain.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 947128251 277 YRCPISLELMRDPVVVATGQTYDRASIKLWM-DSGHNtCPKTGQTLSHTELIPNR 330
Cdd:cd16643    2 YECPICLMALREPVQTPCGHRFCKACILKSIrEAGHK-CPVDNEPLLENQLFPDN 55

U-box domain, a modified RING finger, found in erythroblast macrophage protein (Emp) and similar proteins; Emp, also known as cell proliferation-inducing gene 5 protein or macrophage erythroblast attacher (MAEA), is a key protein which functions in normal differentiation of erythroid cells and macrophages. It is a potential biomarker for hematopoietic evaluation of Hematopoietic stem cell transplantation (HSCT) patients. Emp was initially identified as a heparin-binding protein involved in the association of erythroblasts with macrophages. It promotes erythroid proliferation and maturation. It also plays an important role in erythroblastic island formation. Absence of Emp leads to failure of erythroblast nuclear extrusion. It is required in definitive erythropoiesis and plays a cell intrinsic role in the erythroid lineage. Emp contains a Lissencephaly type-1-like homology (LisH) motif, a C-terminal to LisH (CTLH) domain, and a RING-like U-box domain at the C-terminus.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 947128251 279 CPISLELMRD---PVVVATGQTYDRASIKLWMDSGHN--TCPKTGQT 320
Cdd:cd16659    5 CRITGEVMNEhnpPLALPNGYVYSEKALEEMAEKNDGkvVCPRTGES 51

N-terminal domain of mixed lineage kinase domain-like protein (MLKL) and similar proteins; MLKL is a pseudokinase that does not have protein kinase activity and plays a key role in tumor necrosis factor (TNF)-induced necroptosis, a programmed cell death process. The model corresponds to the MLKL N-terminal region that reveals a four-helix bundle with an additional helix at the top which is likely key for MLKL function. The N-terminal domain binds directly to phospholipids and induces membrane permeabilization.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 947128251  60 IRKTQLLGVVFEELVRvSNLNSNSSVLFLCLEEMYIVLHNIKILIEDFSNGSKFNLLMQIETVADNFHRLTGELSTLLDV 139
Cdd:cd21037   28 AERVAELLLALEELLE-GKEEDLSPELREALEELERTLEEIKEFVEKISKRSRLKRFLKAKSIAEKLEELNERLDDALQL 106

                 ....
gi 947128251 140 LPLQ 143
Cdd:cd21037  107 FQLA 110

Modified RING finger, HC subclass (C3HC3D-type), found in tumor necrosis factor (TNF) receptor-associated factor 7 (TRAF7) and similar proteins; TRAF7, also known as RING finger and WD repeat-containing protein 1 or RING finger protein 119 (RNF119), is an E3 ubiquitin-protein ligase involved in signal transduction pathways that lead either to activation or repression of NF-kappaB transcription factor by promoting K29-linked ubiquitination of several cellular targets, including the NF-kappaB essential modulator (NEMO) and the p65 subunit of NF-kappaB transcription factor. It is also involved in K29-linked polyubiquitination that has been implicated in lysosomal degradation of proteins. Moreover, TRAF7 is required for K48-linked ubiquitination of p53, a key tumor suppressor and a master regulator of various signaling pathways, such as those related to apoptosis, cell cycle and DNA repair. It is also required for tumor necrosis factor alpha (TNFalpha)-induced Jun N-terminal kinase activation and promotes cell death by regulating polyubiquitination and lysosomal degradation of c-FLIP protein. Furthermore, TRAF7 functions as small ubiquitin-like modifier (SUMO) E3 ligase involved in other post-translational modification, such as sumoylation. It binds to and stimulates sumoylation of the proto-oncogene product c-Myb, a transcription factor regulating proliferation and differentiation of hematopoietic cells. It potentiates MEKK3-induced AP1 and CHOP activation and induces apoptosis. Meanwhile, TRAF7 mediates MyoD1 regulation of the pathway and cell-cycle progression in myoblasts. It also plays a role in Toll-like receptors (TLR) signaling. TRAF7 contains an N-terminal domain with a modified C3HC3D-type RING-HC finger and an adjacent zinc finger, and a unique C-terminal domain that comprises a coiled coil domain and seven WD40 repeats.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|
gi 947128251 272 TIPADYRCPISLELMRDPVVVATGQTYDRASIklwMDSGHNTCPKTGQTL 321
Cdd:cd16644    1 PPSVKLYCPLCQRVFKDPVITSCGHTFCRRCA---LTAPGEKCPVDNMKL 47